Inflammatory links between epilepsy and depression: a review of mechanisms and therapeutic strategies

Depression is the most common psychiatric comorbidity of epilepsy. While antiseizure medications (ASMs) can exacerbate depressive symptoms, depression itself may increase both the frequency and duration of epileptic seizures. The pathophysiological mechanisms underlying epilepsy-depression comorbidi...

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Main Authors: Yu-Qian Shi, He-Cai Yang, Cong He, Yu-Hao Wang, Jia Zheng, Xing-Yi Wang, Fang-Yi Hao, Chu-Wen Feng, Lin Ma, Yue-Hui Zhang, Zheng Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2025.1614297/full
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author Yu-Qian Shi
He-Cai Yang
Cong He
Yu-Hao Wang
Jia Zheng
Xing-Yi Wang
Fang-Yi Hao
Chu-Wen Feng
Lin Ma
Yue-Hui Zhang
Zheng Liu
author_facet Yu-Qian Shi
He-Cai Yang
Cong He
Yu-Hao Wang
Jia Zheng
Xing-Yi Wang
Fang-Yi Hao
Chu-Wen Feng
Lin Ma
Yue-Hui Zhang
Zheng Liu
author_sort Yu-Qian Shi
collection DOAJ
description Depression is the most common psychiatric comorbidity of epilepsy. While antiseizure medications (ASMs) can exacerbate depressive symptoms, depression itself may increase both the frequency and duration of epileptic seizures. The pathophysiological mechanisms underlying epilepsy-depression comorbidity (EDC) involve neurotransmitter imbalance, inflammatory responses, oxidative stress (OS), gut microbiota dysbiosis, and neuroendocrine abnormalities. Recent studies highlight that inflammation contributes to EDC via multiple interconnected mechanisms, including glial cell activation, cytokine release, pyroptosis, and oxidative damage, ultimately leading to synaptic dysfunction and neuroimmune imbalance. Drawing from representative and recent evidence, this review summarizes the role of inflammation in the pathogenesis and progression of EDC. It also outlines current inflammation-targeted therapeutic strategies, such as anti-inflammatory drugs, antioxidants, herbal medicine, acupuncture, probiotic modulation, and precision therapies. This review provides a conceptual framework for understanding inflammation-mediated EDC and offers insights into targeted treatment approaches.
format Article
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institution Kabale University
issn 1662-453X
language English
publishDate 2025-06-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Neuroscience
spelling doaj-art-e9bdfabf88df4595b6e88c3496f606902025-08-20T03:30:33ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-06-011910.3389/fnins.2025.16142971614297Inflammatory links between epilepsy and depression: a review of mechanisms and therapeutic strategiesYu-Qian Shi0He-Cai Yang1Cong He2Yu-Hao Wang3Jia Zheng4Xing-Yi Wang5Fang-Yi Hao6Chu-Wen Feng7Lin Ma8Yue-Hui Zhang9Zheng Liu10First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, ChinaFirst Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, ChinaThe Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, ChinaFirst Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, ChinaFirst Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, ChinaFirst Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, ChinaFirst Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, ChinaThe First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, ChinaThe First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, ChinaThe First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, ChinaThe First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, ChinaDepression is the most common psychiatric comorbidity of epilepsy. While antiseizure medications (ASMs) can exacerbate depressive symptoms, depression itself may increase both the frequency and duration of epileptic seizures. The pathophysiological mechanisms underlying epilepsy-depression comorbidity (EDC) involve neurotransmitter imbalance, inflammatory responses, oxidative stress (OS), gut microbiota dysbiosis, and neuroendocrine abnormalities. Recent studies highlight that inflammation contributes to EDC via multiple interconnected mechanisms, including glial cell activation, cytokine release, pyroptosis, and oxidative damage, ultimately leading to synaptic dysfunction and neuroimmune imbalance. Drawing from representative and recent evidence, this review summarizes the role of inflammation in the pathogenesis and progression of EDC. It also outlines current inflammation-targeted therapeutic strategies, such as anti-inflammatory drugs, antioxidants, herbal medicine, acupuncture, probiotic modulation, and precision therapies. This review provides a conceptual framework for understanding inflammation-mediated EDC and offers insights into targeted treatment approaches.https://www.frontiersin.org/articles/10.3389/fnins.2025.1614297/fullepilepsy-depression comorbidityneuroinflammationgut-brain axisnatural anti-inflammatory agentsaging-related inflammation
spellingShingle Yu-Qian Shi
He-Cai Yang
Cong He
Yu-Hao Wang
Jia Zheng
Xing-Yi Wang
Fang-Yi Hao
Chu-Wen Feng
Lin Ma
Yue-Hui Zhang
Zheng Liu
Inflammatory links between epilepsy and depression: a review of mechanisms and therapeutic strategies
Frontiers in Neuroscience
epilepsy-depression comorbidity
neuroinflammation
gut-brain axis
natural anti-inflammatory agents
aging-related inflammation
title Inflammatory links between epilepsy and depression: a review of mechanisms and therapeutic strategies
title_full Inflammatory links between epilepsy and depression: a review of mechanisms and therapeutic strategies
title_fullStr Inflammatory links between epilepsy and depression: a review of mechanisms and therapeutic strategies
title_full_unstemmed Inflammatory links between epilepsy and depression: a review of mechanisms and therapeutic strategies
title_short Inflammatory links between epilepsy and depression: a review of mechanisms and therapeutic strategies
title_sort inflammatory links between epilepsy and depression a review of mechanisms and therapeutic strategies
topic epilepsy-depression comorbidity
neuroinflammation
gut-brain axis
natural anti-inflammatory agents
aging-related inflammation
url https://www.frontiersin.org/articles/10.3389/fnins.2025.1614297/full
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